Differences in hippocampal protein levels between C57Bl/6J, PWD/PhJ, and Apodemus sylvaticus are paralleled by differences in spatial memory.

There is a significant strain-dependent performance in the Morris water maze (MWM), a paradigm for the evaluation of spatial memory. In contrast, information on molecular differences that may be responsible for differences in spatial memory performance is limited. The aim of the study was therefore to investigate differences in hippocampal protein levels in three groups with different performance in the MWM. C57BL/6J (inbred laboratory strain), PWD/PhJ (inbred strain derived from wild animals of Mus musculus), and Apodemus sylvaticus (AS, genus Apodemus) mice were used for the experiments. Proteins from hippocampi, obtained from a behavioral study on these animals, were extracted and run on two-dimensional gel electrophoresis. Proteins spots were quantified, and spots with significantly different levels were identified by mass spectrometry using an ion trap. A series of 49 proteins from different pathways and cascades (signaling, neuronal network, protein synthesis, secretion and degradation, and antioxidant system; intermediary, fat, and carbohydrate metabolism) were significantly different among hippocampi at the stringent statistical level of P ≤ 0.001. These findings are paralleled by differences in the spatial navigation abilities between the strains within the species Mus musculus (C57BL/6 vs. PWD/PhJ) and between the genera Mus and Apodemus. As shown previously, AS learned the task in the MWM and showed good memory retention when tested at the probe trial (day 12), whereas C57BL/6J learned the task, but failed at the probe trial at day 12 as well as PWD/PhJ that failed to learn the task and failed at the probe trial at day 12. A list of above-mentioned proteins were different between PWD/PhJ with bad and AS with good memory retention and may therefore be related to performance in the MWM and thus to spatial memory formation. The experimental approach, however, does not allow discriminating between differences in protein levels a priori and different protein levels induced by the MWM testing. © 2010 Wiley-Liss, Inc.